Drug Interaction Report

Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of ensifentrine. According to the prescribing information, ensifentrine's primary routes of metabolism are oxidative (hydroxylation and O-demethylation) followed by conjugation. Additionally, in vitro data indicates ensifentrine is predominantly metabolized by CYP450 2C9, and to a lesser extent by CYP450 2D6. When ensifentrine (3 mg single dose) was coadministered with the CYP450 2C9 inhibitor fluconazole (200 mg twice daily) to 28 healthy volunteers, ensifentrine systemic exposure (AUC) increased by 1.6-fold and peak plasma concentration (Cmax) increased by 1.4-fold. The increase in ensifentrine exposure by fluconazole was not considered clinically relevant.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.